This Competing Continuation Application for a Ruth L. Kirschstein Institutional National Research Service Award (T32) is focused on the postdoctoral training of M.D., M.D.-Ph.D., and Ph.D. candidates to prepare them to pursue independent careers as successful Clinician-Scientists and/or Biomedical Research Scientists, whose primary interest is the cellular and molecular mechanisms of human disease. Its primary training goal is the development of core research competencies through both informal and structured didactic exercises, coupled with an indepth mentored research experience, in a nurturing and supportive academic medical center environment. The programmatic emphasis is on understanding the basic pathogenetic mechanisms underlying major disease processes that affect the cardiovascular, pulmonary, hematopoietic and immune systems, through the application of the multidisciplinary research tools and strategies of modern cellular and molecular biology, immunology, genetics and genomics, integrative physiology and bioinformatics. The current Training Program, sponsored by the National Heart, Lung and Blood Institute, has been in continuous existence since 1958, and is based in the Department of Pathology at the Brigham and Women's Hospital, a primary teaching affiliate of Harvard Medical School (HMS). While the Training Program's Core Faculty is comprised primarily of clinician-scientists and basic biomedical researchers in the Department of Pathology, trainees also, are encouraged to avail themselves of a wide spectrum of opportunities afforded by research mentors/laboratories in the Longwood Medical Area, including HMS basic science departments (e.g., Pathology, Cell Biology, Systems Biology), the Dana-Farber Cancer Center, the Beth Israel-Deaconess Medical Center, the Harvard-Partners Center for Human Genetics and Genomics, and the Harvard-MIT Health Sciences and Technology Program. Trainees are selected from a national pool of applicants, and the Program's emphasis is on a research training experience tailored to a given candidate's background, scientific interests and career goals.